NEW YORK (AP) — The Vatican is taking the unusual step of conducting a worldwide survey on how parishes deal with sensitive issues such as contraception, divorce and gay couples.
The survey asks how priests minister to same-sex couples and their children — and to men and women living together outside of marriage.
The poll was sent in mid-October to every national bishops conference with instructions to get the widest possible response. The information is for a major meeting on the family that Pope Francis plans next year.
The National Catholic Reporter was first to report the survey Thursday. A U.S. bishops' spokeswoman told The Associated Press the document is authentic and each bishop will decide how to get input.
In England, bishops posted the survey online asking church members to participate.
Newly identified proteins make promising targets for blocking graft-vs.-host disease
PUBLIC RELEASE DATE:
31-Oct-2013
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Contact: Nicole Fawcett nfawcett@umich.edu 734-764-2220 University of Michigan Health System
Finding could help improve outcomes from bone marrow transplants
ANN ARBOR, Mich. Researchers from the University of Michigan Comprehensive Cancer Center have identified new proteins that control the function of critical immune cell subsets called T-cells, which are responsible for a serious and often deadly side effect of lifesaving bone marrow transplants.
These new proteins have not previously been associated with T-cell responses. T-cells help fight infections but also can trigger autoimmune diseases or graft vs. host disease, a side effect of bone marrow transplant in which the new donor cells begin attacking other cells in the patient's body.
"We identified new targets within the T-cells that regulate the immune response to foreign antigens. If these proteins can be targeted, it may prove helpful in reducing graft-vs.-host disease," says study first author Yaping Sun, M.D., Ph.D., internal medicine research investigator at the U-M Medical School.
Reducing the incidence of graft-vs.-host disease could make bone marrow transplant an option for more people with blood-based cancers. About half of people who receive a transplant from donated cells develop graft-vs.-host.
In this study, which is published in the Journal of Clinical Investigation, the researchers looked at the landscape of mRNA and micro-RNA after the T-cells were activated by different kinds of stimuli. mRNA are made from the genes present in the DNA and serve as templates for making proteins. Micro-RNA are also copied from the DNA but do not code for proteins; instead they fine tune the expression of other genes and proteins.
By looking at both simultaneously, the researchers were able to tease out only the mRNAs that were regulated by micro-RNA. They found that two mRNA's that express the proteins Wapal and Synj1 were among the most differentially expressed. Both these proteins have been implicated in other cellular functions, but had not previously been linked to a role in T-cell immune responses.
The researchers validated their findings in laboratory studies to look at T-cell functions in cell cultures and in mice. Importantly, when they blocked the proteins, it impacted the T-cell function and reduced graft-vs.-host disease in mice.
"We know a lot of proteins play a role in T-cell responses. We're adding more to the armory. Our initial validations in mice are preliminary, but a promising start," says senior study author Pavan Reddy, M.D., professor of hematology/oncology at the U-M Medical School.
This research is still in its early stages. No compounds currently are known to target Wapal or Synj1. Additional research is needed.
###
Additional authors: Isao Tawara, Mie University Hospital, Japan; Meng Zhao and Zhaohui S. Qin, Emory University; Tomomi Toubai, Nathan Mathewson, Hiroya Tamaki, Evelyn Nieves, and Arul Chinnaiyan, University of Michigan
Funding: National Institutes of Health grants AI-075284, CA-173878 and HL-090775; clinical research award from the Leukemia Lymphoma Society; basic science investigator award from the American Society of Transplantation
Disclosure: None
Reference:Journal of Clinical Investigation, Vol. 123, No. 11, November 2013
Resources:
U-M Cancer AnswerLine, 800-865-1125
U-M Comprehensive Cancer Center, http://www.mcancer.org
Clinical trials at U-M, http://www.mcancer.org/clinicaltrials
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Newly identified proteins make promising targets for blocking graft-vs.-host disease
PUBLIC RELEASE DATE:
31-Oct-2013
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Contact: Nicole Fawcett nfawcett@umich.edu 734-764-2220 University of Michigan Health System
Finding could help improve outcomes from bone marrow transplants
ANN ARBOR, Mich. Researchers from the University of Michigan Comprehensive Cancer Center have identified new proteins that control the function of critical immune cell subsets called T-cells, which are responsible for a serious and often deadly side effect of lifesaving bone marrow transplants.
These new proteins have not previously been associated with T-cell responses. T-cells help fight infections but also can trigger autoimmune diseases or graft vs. host disease, a side effect of bone marrow transplant in which the new donor cells begin attacking other cells in the patient's body.
"We identified new targets within the T-cells that regulate the immune response to foreign antigens. If these proteins can be targeted, it may prove helpful in reducing graft-vs.-host disease," says study first author Yaping Sun, M.D., Ph.D., internal medicine research investigator at the U-M Medical School.
Reducing the incidence of graft-vs.-host disease could make bone marrow transplant an option for more people with blood-based cancers. About half of people who receive a transplant from donated cells develop graft-vs.-host.
In this study, which is published in the Journal of Clinical Investigation, the researchers looked at the landscape of mRNA and micro-RNA after the T-cells were activated by different kinds of stimuli. mRNA are made from the genes present in the DNA and serve as templates for making proteins. Micro-RNA are also copied from the DNA but do not code for proteins; instead they fine tune the expression of other genes and proteins.
By looking at both simultaneously, the researchers were able to tease out only the mRNAs that were regulated by micro-RNA. They found that two mRNA's that express the proteins Wapal and Synj1 were among the most differentially expressed. Both these proteins have been implicated in other cellular functions, but had not previously been linked to a role in T-cell immune responses.
The researchers validated their findings in laboratory studies to look at T-cell functions in cell cultures and in mice. Importantly, when they blocked the proteins, it impacted the T-cell function and reduced graft-vs.-host disease in mice.
"We know a lot of proteins play a role in T-cell responses. We're adding more to the armory. Our initial validations in mice are preliminary, but a promising start," says senior study author Pavan Reddy, M.D., professor of hematology/oncology at the U-M Medical School.
This research is still in its early stages. No compounds currently are known to target Wapal or Synj1. Additional research is needed.
###
Additional authors: Isao Tawara, Mie University Hospital, Japan; Meng Zhao and Zhaohui S. Qin, Emory University; Tomomi Toubai, Nathan Mathewson, Hiroya Tamaki, Evelyn Nieves, and Arul Chinnaiyan, University of Michigan
Funding: National Institutes of Health grants AI-075284, CA-173878 and HL-090775; clinical research award from the Leukemia Lymphoma Society; basic science investigator award from the American Society of Transplantation
Disclosure: None
Reference:Journal of Clinical Investigation, Vol. 123, No. 11, November 2013
Resources:
U-M Cancer AnswerLine, 800-865-1125
U-M Comprehensive Cancer Center, http://www.mcancer.org
Clinical trials at U-M, http://www.mcancer.org/clinicaltrials
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Racism linked with gun ownership and opposition to gun control in white Americans
PUBLIC RELEASE DATE:
31-Oct-2013
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Contact: Alison Barbuti alison.barbuti@manchester.ac.uk 44-016-127-58383 University of Manchester
A new study has found that higher levels of racism in white Americans is associated with having a gun in the home and greater opposition to gun control policies.
The research, published in PLoS One, was led by Dr Kerry O'Brien from The University of Manchester and Monash University and used data from a large representative sample of white US voters.
After accounting for numerous other factors such as income, education and political ideology, the researchers found that for each one point increase (on a scale from one to five) in symbolic racism there was a 50 percent increase in the odds of having a gun in the home and a 28 percent increase in support for policies allowing people to carry concealed guns.
Each one point increase in symbolic racism (a modern measure of anti-black racism) was also associated with a 27 percent increase in the odds of opposing bans on hand guns in the home. After accounting for those who already had a gun in the home, the odds were reduced to a non-significant 17 percent increase. However, the authors note that this reduction is unsurprising as opposition to bans on guns equates to self interest on behalf of those who already own a gun and do not wish to give it up. And racism was already strongly associated with having a gun in the home.
The research was stimulated by gun control debates in the US after mass shootings such as the Sandy Hook tragedy, and research showing that with all things being equal black Americans are more likely to be shot than whites. The most recent figures show that there are approximately 38,000 gun related deaths in the US each year. With other research suggesting that having a gun in the home is related to a 2.7 and 4.8 fold increase in the risk of a member of that home dying from homicide or suicide, respectively.
Dr O'Brien said: "Coming from countries with strong gun control policies, and a 30-fold lower rate of gun-related homicides, we found the arguments for opposing gun control counterintuitive and somewhat illogical. For example, US whites oppose gun control to a far greater extent than do blacks, but whites are actually more likely to kill themselves with their guns, than be killed by someone else. Why would you keep them? So we decided to examine what social and psychological factors predict gun ownership and opposition to gun control."
Conservatism, anti-government sentiment, party identification, being from a southern state, were also associated with opposition to gun controls, but the association between racism and the gun-related outcomes remained after accounting for these factors and other participant characteristics (age, education, income, gender).
Symbolic racism supplanted old-fashioned or overt/blatant racism which was associated with open support for race inequality and segregation under 'Jim Crow Laws', but it still captures the anti-black sentiment and traditional values that underpinned blatant racism. Symbolic racism has also been found to be related to stronger opposition to policies that may benefit blacks (e.g. welfare), and greater support for policies that seem to disadvantage blacks (e.g. longer prison sentences).
Study co-author Dr Dermot Lynott, from Lancaster University, said: "We were initially surprised that no one had studied this issue before; however, the US government cut research funding for gun-related research over decade and a half ago, so research in this area has been somewhat suppressed."
Dr O'Brien said: "According to a Pew Research Center report the majority of white Americans support stricter gun control, but the results of our study suggest that those who oppose gun reform tend to have a stronger racial bias, tend to be politically and ideologically conservative and from southern states, and have higher anti-government sentiment."
He added: "The study is a first step, but there needs to be more investment in empirical research around how racial bias may influence people's policy decisions, particularly those policies that impact on the health and wellbeing of US citizens."
###
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Racism linked with gun ownership and opposition to gun control in white Americans
PUBLIC RELEASE DATE:
31-Oct-2013
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Contact: Alison Barbuti alison.barbuti@manchester.ac.uk 44-016-127-58383 University of Manchester
A new study has found that higher levels of racism in white Americans is associated with having a gun in the home and greater opposition to gun control policies.
The research, published in PLoS One, was led by Dr Kerry O'Brien from The University of Manchester and Monash University and used data from a large representative sample of white US voters.
After accounting for numerous other factors such as income, education and political ideology, the researchers found that for each one point increase (on a scale from one to five) in symbolic racism there was a 50 percent increase in the odds of having a gun in the home and a 28 percent increase in support for policies allowing people to carry concealed guns.
Each one point increase in symbolic racism (a modern measure of anti-black racism) was also associated with a 27 percent increase in the odds of opposing bans on hand guns in the home. After accounting for those who already had a gun in the home, the odds were reduced to a non-significant 17 percent increase. However, the authors note that this reduction is unsurprising as opposition to bans on guns equates to self interest on behalf of those who already own a gun and do not wish to give it up. And racism was already strongly associated with having a gun in the home.
The research was stimulated by gun control debates in the US after mass shootings such as the Sandy Hook tragedy, and research showing that with all things being equal black Americans are more likely to be shot than whites. The most recent figures show that there are approximately 38,000 gun related deaths in the US each year. With other research suggesting that having a gun in the home is related to a 2.7 and 4.8 fold increase in the risk of a member of that home dying from homicide or suicide, respectively.
Dr O'Brien said: "Coming from countries with strong gun control policies, and a 30-fold lower rate of gun-related homicides, we found the arguments for opposing gun control counterintuitive and somewhat illogical. For example, US whites oppose gun control to a far greater extent than do blacks, but whites are actually more likely to kill themselves with their guns, than be killed by someone else. Why would you keep them? So we decided to examine what social and psychological factors predict gun ownership and opposition to gun control."
Conservatism, anti-government sentiment, party identification, being from a southern state, were also associated with opposition to gun controls, but the association between racism and the gun-related outcomes remained after accounting for these factors and other participant characteristics (age, education, income, gender).
Symbolic racism supplanted old-fashioned or overt/blatant racism which was associated with open support for race inequality and segregation under 'Jim Crow Laws', but it still captures the anti-black sentiment and traditional values that underpinned blatant racism. Symbolic racism has also been found to be related to stronger opposition to policies that may benefit blacks (e.g. welfare), and greater support for policies that seem to disadvantage blacks (e.g. longer prison sentences).
Study co-author Dr Dermot Lynott, from Lancaster University, said: "We were initially surprised that no one had studied this issue before; however, the US government cut research funding for gun-related research over decade and a half ago, so research in this area has been somewhat suppressed."
Dr O'Brien said: "According to a Pew Research Center report the majority of white Americans support stricter gun control, but the results of our study suggest that those who oppose gun reform tend to have a stronger racial bias, tend to be politically and ideologically conservative and from southern states, and have higher anti-government sentiment."
He added: "The study is a first step, but there needs to be more investment in empirical research around how racial bias may influence people's policy decisions, particularly those policies that impact on the health and wellbeing of US citizens."
###
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Scientists capture most detailed picture yet of key AIDS protein
PUBLIC RELEASE DATE:
31-Oct-2013
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Contact: Sarah Smith sas2072@med.cornell.edu 646-317-7401 Weill Cornell Medical College
Finding represents a scientific feat and progress towards an HIV vaccine
NEW YORK (October 31, 2013) -- Collaborating scientists at The Scripps Research Institute (TSRI) and Weill Cornell Medical College have determined the first atomic-level structure of the tripartite HIV envelope protein -- long considered one of the most difficult targets in structural biology and of great value for medical science.
The new data provide the most detailed picture yet of the AIDS-causing virus's complex envelope, including sites that future vaccines will try to mimic to elicit a protective immune response.
"Most of the prior structural studies of this envelope complex focused on individual subunits, but we've needed the structure of the full complex to properly define the sites of vulnerability that could be targeted, for example with a vaccine," said Dr. Ian A. Wilson, the Hansen Professor of Structural Biology at TSRI and a senior author of the new research with biologists Drs. Andrew Ward and Bridget Carragher of TSRI and virologist and immunologist Dr. John Moore of Weill Cornell.
The findings were published in two papers in Science Express, the early online edition of the journal Science, on October 31, 2013.
A Difficult Target
HIV, the human immunodeficiency virus, infects about 34 million people globally, 10 percent of whom are children, according to World Health Organization estimates. Although antiviral drugs are now used to manage many HIV infections, especially in developed countries, scientists have long sought a vaccine that can prevent new infections and would help perhaps to ultimately eradicate the virus from the human population.
However, none of the HIV vaccines tested so far has come close to providing adequate protection. This failure is due largely to the challenges posed by HIV's envelope protein, known to virologists as Env.
HIV's Env is not a single, simple protein but rather a "trimer" made of three identical, loosely connected structures with a stalk-like subunit, gp41, and a cap-like region, gp120. Each trimer resembles a mushroom and about 15 of these Env trimers sprout from the membrane of a typical virus particle, ready to latch onto susceptible human cells and facilitate viral entry.
Although Env in principle is exposed to the immune system, in practice it has evolved highly effective strategies for evading immune attack. It frequently mutates its outermost "variable loop" regions, for example, and also coats its surfaces with hard-to-grip sugar molecules called glycans.
Even so, HIV vaccine designers might have succeeded by now had they been able to study the structure of the entire Env protein at atomic-scale--in particular, to fully characterize the sites where the most effective virus-neutralizing antibodies bind. But Env's structure is so complex and delicate that scientists have had great difficulty obtaining the protein in a form that is suitable for atomic-resolution imaging.
"It tends to fall apart, for example, even when it's on the surface of the virus, so to study it we have to engineer it to be more stable," said Dr. Ward, who is an assistant professor in TSRI's Department of Integrative Structural and Computational Biology.
The key goal in this area has been to engineer a version of the Env trimer that has the stability and other properties needed for atomic-resolution imaging, yet retains virtually all of the complex structural characteristics of native Env.
Imaging Env
After many years in pursuit of this goal, Drs. Moore, Rogier W. Sanders and their colleagues at Weill Cornell, working with Drs. Wilson, Ward and others at TSRI, recently managed to produce a version of the Env trimer (called BG505 SOSIP.664 gp140) that is suitable for atomic-level imaging work--and includes all of the trimer structure that normally sits outside the viral membrane. The TSRI researchers then evaluated the new Env trimer using advanced versions of two imaging methods, X-ray crystallography and electron microscopy. The X-ray crystallography study was the first ever of an Env trimer, and both methods resolved the trimer structure to a finer level of detail than has been reported before.
"The new data are consistent with the findings on Env subunits over the last 15 years, but also have enabled us to explain many prior observations about HIV in structural terms for the first time," said Dr. Jean-Philippe Julien, a senior research associate in the Wilson laboratory at TSRI, who was first author of the X-ray crystallography study.
The data illuminated the complex process by which the Env trimer assembles and later undergoes radical shape changes during infection and clarified how it compares to envelope proteins on other dangerous viruses, such as flu and Ebola.
Arguably the most important implications of the new findings are for HIV vaccine design. In both of the new studies, Env trimers were imaged while bound to broadly neutralizing antibodies against HIV. Such antibodies, isolated from naturally infected patients, are the very rare ones that somehow bind to Env in a way that blocks the infectivity of a high proportion of HIV strains.
Ideally an HIV vaccine would elicit large numbers of such antibodies from patients, and to achieve that, vaccine designers would like to know the precise structural details of the sites where these antibodies bind to the virus--so that they can mimic those viral "epitopes" with the vaccine.
"It's been a privilege for us to work with the Scripps' team on this project," said Dr. Moore, a professor of microbiology and immunology at Weill Cornell. "Now we all need to harness this new knowledge to design and test next-generation trimers and see if we can induce the broadly active neutralizing antibodies that an effective vaccine is going to need."
"One surprise from this study was the revelation of the complexity and the relative inaccessibility of these neutralizing epitopes," Dr. Julien added. "It helps to know this for future vaccine design, but it also makes it clear why previous structure-based HIV vaccines have had so little success."
"We found that these neutralizing epitopes encompass features such as the variable loop regions and glycans that were excluded from previous studies of individual Env subunits," said Dmitry Lyumkis, first author of the electron microscopy study, who is a graduate student at TSRI participating in the NIH-funded National Resource for Automated Molecular Microscopy. "We observed, too, that neutralizing antibody binding to gp120 can be influenced by the neighboring gp120 structure within the trimer--another complication that was not apparent when we were not studying the whole trimer."
Having provided these valuable structural insights, the new Env trimer is now being put to work in vaccine development. "We and others are already injecting the trimer into animals to elicit antibodies," Dr. Ward said. "We can look at the antibodies that are generated and if necessary modify the Env trimer structure and try again. In this iterative way, we aim to refine and increase the antibody response in the animals and eventually, humans."
###
Other contributors to the studies, "Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 Env trimer," and "Crystal structure of a soluble cleaved HIV-1 envelope trimer in complex with a glycan-dependent broadly neutralizing antibody," included TSRI's Natalia de Val, Devin Sok, Drs. Robyn L. Stanfield and Marc C. Deller; and Weill Cornell Medical College's Albert Cupo and Dr. Per-Johan Klasse. In addition to Drs. Wilson, Ward and Carragher, senior participants at TSRI included Drs. Clinton S. Potter and Dennis Burton.
The research was supported in part by the National Institutes of Health (HIVRAD P01 AI82362, R01 AI36082, R01 AI084817, R37 AI36082, R01 AI33292), the NIH's National Institute of General Medical Sciences (GM103310) and the International AIDS Vaccine Initiative Neutralizing Antibody Consortium. IAVI has filed a patent that includes WCMC and TSRI authors on the development of the BG505 SOSIP.664 trimers as vaccine antigens.
Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with Houston Methodist. For more information, visit weill.cornell.edu.
Office of External Affairs
Weill Cornell Medical College
tel: 646.317.7401
email: pr@med.cornell.edu
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Scientists capture most detailed picture yet of key AIDS protein
PUBLIC RELEASE DATE:
31-Oct-2013
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Contact: Sarah Smith sas2072@med.cornell.edu 646-317-7401 Weill Cornell Medical College
Finding represents a scientific feat and progress towards an HIV vaccine
NEW YORK (October 31, 2013) -- Collaborating scientists at The Scripps Research Institute (TSRI) and Weill Cornell Medical College have determined the first atomic-level structure of the tripartite HIV envelope protein -- long considered one of the most difficult targets in structural biology and of great value for medical science.
The new data provide the most detailed picture yet of the AIDS-causing virus's complex envelope, including sites that future vaccines will try to mimic to elicit a protective immune response.
"Most of the prior structural studies of this envelope complex focused on individual subunits, but we've needed the structure of the full complex to properly define the sites of vulnerability that could be targeted, for example with a vaccine," said Dr. Ian A. Wilson, the Hansen Professor of Structural Biology at TSRI and a senior author of the new research with biologists Drs. Andrew Ward and Bridget Carragher of TSRI and virologist and immunologist Dr. John Moore of Weill Cornell.
The findings were published in two papers in Science Express, the early online edition of the journal Science, on October 31, 2013.
A Difficult Target
HIV, the human immunodeficiency virus, infects about 34 million people globally, 10 percent of whom are children, according to World Health Organization estimates. Although antiviral drugs are now used to manage many HIV infections, especially in developed countries, scientists have long sought a vaccine that can prevent new infections and would help perhaps to ultimately eradicate the virus from the human population.
However, none of the HIV vaccines tested so far has come close to providing adequate protection. This failure is due largely to the challenges posed by HIV's envelope protein, known to virologists as Env.
HIV's Env is not a single, simple protein but rather a "trimer" made of three identical, loosely connected structures with a stalk-like subunit, gp41, and a cap-like region, gp120. Each trimer resembles a mushroom and about 15 of these Env trimers sprout from the membrane of a typical virus particle, ready to latch onto susceptible human cells and facilitate viral entry.
Although Env in principle is exposed to the immune system, in practice it has evolved highly effective strategies for evading immune attack. It frequently mutates its outermost "variable loop" regions, for example, and also coats its surfaces with hard-to-grip sugar molecules called glycans.
Even so, HIV vaccine designers might have succeeded by now had they been able to study the structure of the entire Env protein at atomic-scale--in particular, to fully characterize the sites where the most effective virus-neutralizing antibodies bind. But Env's structure is so complex and delicate that scientists have had great difficulty obtaining the protein in a form that is suitable for atomic-resolution imaging.
"It tends to fall apart, for example, even when it's on the surface of the virus, so to study it we have to engineer it to be more stable," said Dr. Ward, who is an assistant professor in TSRI's Department of Integrative Structural and Computational Biology.
The key goal in this area has been to engineer a version of the Env trimer that has the stability and other properties needed for atomic-resolution imaging, yet retains virtually all of the complex structural characteristics of native Env.
Imaging Env
After many years in pursuit of this goal, Drs. Moore, Rogier W. Sanders and their colleagues at Weill Cornell, working with Drs. Wilson, Ward and others at TSRI, recently managed to produce a version of the Env trimer (called BG505 SOSIP.664 gp140) that is suitable for atomic-level imaging work--and includes all of the trimer structure that normally sits outside the viral membrane. The TSRI researchers then evaluated the new Env trimer using advanced versions of two imaging methods, X-ray crystallography and electron microscopy. The X-ray crystallography study was the first ever of an Env trimer, and both methods resolved the trimer structure to a finer level of detail than has been reported before.
"The new data are consistent with the findings on Env subunits over the last 15 years, but also have enabled us to explain many prior observations about HIV in structural terms for the first time," said Dr. Jean-Philippe Julien, a senior research associate in the Wilson laboratory at TSRI, who was first author of the X-ray crystallography study.
The data illuminated the complex process by which the Env trimer assembles and later undergoes radical shape changes during infection and clarified how it compares to envelope proteins on other dangerous viruses, such as flu and Ebola.
Arguably the most important implications of the new findings are for HIV vaccine design. In both of the new studies, Env trimers were imaged while bound to broadly neutralizing antibodies against HIV. Such antibodies, isolated from naturally infected patients, are the very rare ones that somehow bind to Env in a way that blocks the infectivity of a high proportion of HIV strains.
Ideally an HIV vaccine would elicit large numbers of such antibodies from patients, and to achieve that, vaccine designers would like to know the precise structural details of the sites where these antibodies bind to the virus--so that they can mimic those viral "epitopes" with the vaccine.
"It's been a privilege for us to work with the Scripps' team on this project," said Dr. Moore, a professor of microbiology and immunology at Weill Cornell. "Now we all need to harness this new knowledge to design and test next-generation trimers and see if we can induce the broadly active neutralizing antibodies that an effective vaccine is going to need."
"One surprise from this study was the revelation of the complexity and the relative inaccessibility of these neutralizing epitopes," Dr. Julien added. "It helps to know this for future vaccine design, but it also makes it clear why previous structure-based HIV vaccines have had so little success."
"We found that these neutralizing epitopes encompass features such as the variable loop regions and glycans that were excluded from previous studies of individual Env subunits," said Dmitry Lyumkis, first author of the electron microscopy study, who is a graduate student at TSRI participating in the NIH-funded National Resource for Automated Molecular Microscopy. "We observed, too, that neutralizing antibody binding to gp120 can be influenced by the neighboring gp120 structure within the trimer--another complication that was not apparent when we were not studying the whole trimer."
Having provided these valuable structural insights, the new Env trimer is now being put to work in vaccine development. "We and others are already injecting the trimer into animals to elicit antibodies," Dr. Ward said. "We can look at the antibodies that are generated and if necessary modify the Env trimer structure and try again. In this iterative way, we aim to refine and increase the antibody response in the animals and eventually, humans."
###
Other contributors to the studies, "Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 Env trimer," and "Crystal structure of a soluble cleaved HIV-1 envelope trimer in complex with a glycan-dependent broadly neutralizing antibody," included TSRI's Natalia de Val, Devin Sok, Drs. Robyn L. Stanfield and Marc C. Deller; and Weill Cornell Medical College's Albert Cupo and Dr. Per-Johan Klasse. In addition to Drs. Wilson, Ward and Carragher, senior participants at TSRI included Drs. Clinton S. Potter and Dennis Burton.
The research was supported in part by the National Institutes of Health (HIVRAD P01 AI82362, R01 AI36082, R01 AI084817, R37 AI36082, R01 AI33292), the NIH's National Institute of General Medical Sciences (GM103310) and the International AIDS Vaccine Initiative Neutralizing Antibody Consortium. IAVI has filed a patent that includes WCMC and TSRI authors on the development of the BG505 SOSIP.664 trimers as vaccine antigens.
Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with Houston Methodist. For more information, visit weill.cornell.edu.
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Leading cause of heart disease ignored in North America's poorest communities
PUBLIC RELEASE DATE:
31-Oct-2013
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Contact: Deborah Elson deborah.elson@sabin.org 202-621-1691 Public Library of Science
Inaction has jeopardized the health and economic well-being of millions
A leading cause of heart disease remains overlooked in North America's most impoverished communities, researchers said today in an editorial published in PLOS Neglected Tropical Diseases. Chagas disease has rendered a heavy health and economic toll, yet insufficient political and medical support for gathering specific data, providing diagnosis and treatment, and developing new tools has impeded much-needed breakthroughs.
"We have already identified critical steps to save lives and make breakthroughs in Chagas disease control in North America," said Dr. Peter Hotez, the editorial's lead author, director of the Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development and dean of the National School of Tropical Medicine at Baylor College of Medicine. "This is an achievable public health goal that will also reduce the disease's detrimental economic burden. Greater medical awareness, scientific cooperation between key countries, and public-private partnerships will help us beat this scourge."
Chagas disease is a parasitic infection most commonly transmitted through blood-feeding triatomine bugs, but it can also be spread through pregnancy, blood transfusion, and contaminated food or drink. Up to 30% of infections result in debilitating and life-threatening heart disease and severe intestinal and liver complications. People living in extremely impoverished communities are most vulnerable because of poor-quality housing and inadequate access to health care, education and vector control.
Chagas disease infects an estimated 10 million people worldwide; however, much less is known about the true disease burden in North America. According to some preliminary estimates, Mexico ranks third, and the United States seventh, in terms of the number of infected individuals with Chagas disease in the Western Hemisphere, where 99% of the cases occur.
It is also estimated that 40,000 pregnant North American women may be infected with T. cruzi at any given time, resulting in 2,000 congenital cases through mother-to-child transmission.
A lack of facilities offering diagnosis and treatment of Chagas disease has prevented at-risk and infected people from receiving the critical and often life-saving attention they need. While two drug treatments currently exist, they cause undesirable adverse effects, are unsafe for pregnant women and are not approved for use in the United States.
"The research community is pushing science as hard as possible to ensure we get new treatments to people living with Chagas disease, but we need to ensure that governments prioritize the disease," said Dr. Bernard Pecoul, a co-author of the editorial and Executive Director of the Drugs for Neglected Diseases initiative (DNDi). "It is urgent to diagnose and treat patients with what we have available today, until research and development efforts deliver true breakthroughs for the millions in need." DNDi has produced a pediatric dosage form of benznidazole for children with Chagas disease, and is currently developing new drug candidates for a truly novel, safe, effective and affordable treatment for all patients.
The Sabin Vaccine Institute's Product Development Partnership (Sabin PDP), in partnership with Baylor College of Medicine and Texas Children's Hospital and with support from the Slim Initiative for the Development of Neglected Tropical Diseases and from the Southwest Electronic Energy Medical Research, has initiated development for a new therapeutic vaccine.
###
In addition to Dr. Hotez and Dr. Pecoul, the paper's authors include Eric Dumonteil, Autonomous University of Yucatan (UADY); Miguel Betancourt Cravioto, Carlos Slim Health Institute; Maria Elena Bottazzi, National School of Tropical Medicine at Baylor College of Medicine and the Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; Roberto Tapia-Conyer, Carlos Slim Health Institute; Sheba Meymandi, Olive View-UCLA Medical Center; Unni Karunakara, Medecins Sans Frontiers/Doctors Without Borders; Isabela Ribeiro, DNDi; and Rachel M. Cohen, DNDi.
PLEASE ADD THE FOLLOWING LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002300
(Link will go live upon embargo lift)
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Leading cause of heart disease ignored in North America's poorest communities
PUBLIC RELEASE DATE:
31-Oct-2013
[
| E-mail
]
Share
Contact: Deborah Elson deborah.elson@sabin.org 202-621-1691 Public Library of Science
Inaction has jeopardized the health and economic well-being of millions
A leading cause of heart disease remains overlooked in North America's most impoverished communities, researchers said today in an editorial published in PLOS Neglected Tropical Diseases. Chagas disease has rendered a heavy health and economic toll, yet insufficient political and medical support for gathering specific data, providing diagnosis and treatment, and developing new tools has impeded much-needed breakthroughs.
"We have already identified critical steps to save lives and make breakthroughs in Chagas disease control in North America," said Dr. Peter Hotez, the editorial's lead author, director of the Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development and dean of the National School of Tropical Medicine at Baylor College of Medicine. "This is an achievable public health goal that will also reduce the disease's detrimental economic burden. Greater medical awareness, scientific cooperation between key countries, and public-private partnerships will help us beat this scourge."
Chagas disease is a parasitic infection most commonly transmitted through blood-feeding triatomine bugs, but it can also be spread through pregnancy, blood transfusion, and contaminated food or drink. Up to 30% of infections result in debilitating and life-threatening heart disease and severe intestinal and liver complications. People living in extremely impoverished communities are most vulnerable because of poor-quality housing and inadequate access to health care, education and vector control.
Chagas disease infects an estimated 10 million people worldwide; however, much less is known about the true disease burden in North America. According to some preliminary estimates, Mexico ranks third, and the United States seventh, in terms of the number of infected individuals with Chagas disease in the Western Hemisphere, where 99% of the cases occur.
It is also estimated that 40,000 pregnant North American women may be infected with T. cruzi at any given time, resulting in 2,000 congenital cases through mother-to-child transmission.
A lack of facilities offering diagnosis and treatment of Chagas disease has prevented at-risk and infected people from receiving the critical and often life-saving attention they need. While two drug treatments currently exist, they cause undesirable adverse effects, are unsafe for pregnant women and are not approved for use in the United States.
"The research community is pushing science as hard as possible to ensure we get new treatments to people living with Chagas disease, but we need to ensure that governments prioritize the disease," said Dr. Bernard Pecoul, a co-author of the editorial and Executive Director of the Drugs for Neglected Diseases initiative (DNDi). "It is urgent to diagnose and treat patients with what we have available today, until research and development efforts deliver true breakthroughs for the millions in need." DNDi has produced a pediatric dosage form of benznidazole for children with Chagas disease, and is currently developing new drug candidates for a truly novel, safe, effective and affordable treatment for all patients.
The Sabin Vaccine Institute's Product Development Partnership (Sabin PDP), in partnership with Baylor College of Medicine and Texas Children's Hospital and with support from the Slim Initiative for the Development of Neglected Tropical Diseases and from the Southwest Electronic Energy Medical Research, has initiated development for a new therapeutic vaccine.
###
In addition to Dr. Hotez and Dr. Pecoul, the paper's authors include Eric Dumonteil, Autonomous University of Yucatan (UADY); Miguel Betancourt Cravioto, Carlos Slim Health Institute; Maria Elena Bottazzi, National School of Tropical Medicine at Baylor College of Medicine and the Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development; Roberto Tapia-Conyer, Carlos Slim Health Institute; Sheba Meymandi, Olive View-UCLA Medical Center; Unni Karunakara, Medecins Sans Frontiers/Doctors Without Borders; Isabela Ribeiro, DNDi; and Rachel M. Cohen, DNDi.
PLEASE ADD THE FOLLOWING LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002300
(Link will go live upon embargo lift)
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Brandy Clark's album 12 Stories is so good that you almost think she really could achieve Nashville’s salvation.
Photo by Jason Davis/Getty Images
Brandy Clark has just completed her latest turn in a songwriter’s showcase at Nashville’s Bluebird Café and, for just a second, the room is silent as held breath. Then an ovation sweeps through like a small explosion, an exhalation of pent-up expectations and hopes and “Oh my God, did you hear that?”
I don’t remember for certain which number Clark had just sung—honestly, it might have been any of the songs off her amazing debut album, 12 Stories, released Oct. 22—but I think it was “What Will Keep Me out Heaven.” In that breathtaking piano-and-pedal-steel ballad, Clark plays a woman hesitating before an elevator, torn: The man waiting for her upstairs is married to a woman she doesn’t know and doesn’t wish to hurt—but then again she’s come to realize that she’s married to a stranger herself; that’s why she’s here. The lyric leaves her right there, too, undecided, weighing promise and regret—though the tremble and ache in Clark’s voice leaves little doubt she’s headed upstairs.
Clark was joined at the Bluebird that evening by a trio of good friends and fellow songwriters: Trevor Rosen, Josh Osborne, and, seated directly across from Clark for the Sept. 21 in-the-round-performance, Shane McAnally, who’s been on quite a songwriting roll lately. Partnering with several others—Clark, Rosen, Osborne, or the likeminded Kasey Musgraves, often as not—McAnally has co-written hits for Kenny Chesney, Lady Antebellum, Jake Owen, Miranda Lambert, The Band Perry, and Luke Bryan, and has seen dozens more of his songs recorded by Nashville types ranging from Lee Ann Womack to Uncle Cracker, Tim McGraw to Kelly Clarkson to Florida Georgia Line. He is the most successful songwriter Nashville has seen in a generation.
As the applause for Clark shrinks to excited murmurs, McAnally nods in his friend’s direction and says, “That girl’s gonna save this town.”
It was an offhand comment, but, considering the source, it was nearly as jaw-dropping as the performance that inspired it. After all, by the measures that matter most to the Nashville music establishment, Shane McAnally is this town. How can he possibly believe it needs saving?
Concerns about the soul of Nashville or of country music—not the same entities, by any means, but in this case close enough—are hardly new. Choose nearly any period of country you like—Nashville Sound, Urban Cowboy, Garth and Shania’s “Hot New Country,” take your pick—and you’ll find plenty of folks who, upon listening to the latest mainstream version of the genre, declared it in figurative danger of going to hell. But previously these complaints have come from musicians specializing in some sub-style or other that was just then being shut out by country radio—or from the fans who preferred those out-of-fashion sounds—rather than from someone like McAnally, whose work is in heavy commercial rotation, albeit in recordings by other singers.
So what’s the complaint, then? For the past several weeks, the No. 1 spot on Billboard’s Hot Country Songs Chart has been a hard-rocking number with verses that are rapped as much as sung, a hoedown throw-down in which a hyper-macho singer seduces a tanned hottie while drinking a beer and driving his pickup truck down to the river in the moonlight. The record is “That’s My Kind of Night,” by country heartthrob Luke Bryan. But set the action in the afternoon instead, and switch out “beer” for “Southern [Comfort],” and the very same description works for “Cruise,” the Florida Georgia Line hit that topped the same chart for most of this past spring and summer. As it would, with minimal edits, for Blake Shelton’s “The Boys ’Round Here” and Randy Houser’s “How Country Feels” and too-many-to-count other radio hits, big and small, across the past half-decade.
Admittedly, there’s been more to country radio during these last several years than these party-hearty hits. But the songs have dominated playlists to such an extent that it has certainly felt like the format had turned into one never-ending-beer-keg-dirt-road-good-time-I’m-country-truck song. That dominance, to the seeming extinction of almost any other emotion or subject, is the complaint.
WASHINGTON (AP) — The Food and Drug Administration says that almost 7 percent of imported spices over a three-year period were contaminated with salmonella.
In a report released Wednesday, the FDA says testing of imported spices between 2007 and 2010 showed that spices were twice as likely as other inspected foods to be contaminated with the pathogen. More than 80 different types of salmonella were detected.
The agency decided to study the issue as several spice-related outbreaks have caused illnesses around the globe. In 2009 and 2010, black pepper and red pepper from India, Vietnam and China used in salami caused hundreds of illnesses. The FDA says there have been 14 known outbreaks around the world since 1973, causing almost 2,000 illnesses, many of which were in children.
The FDA says that during the three year period, 749 shipments of spice were refused entry into the United States because of salmonella contamination while 238 other shipments were denied because of the presence of what the FDA calls "filth" — insects, excrement, hair or other materials.
The agency said that some of the spices that were found contaminated at the border were later cooked or treated to eliminate possible pathogens, so much of the salmonella was likely gone by the time the spices were eaten. The agency also noted that the amount of spice generally eaten at a meal is small, meaning people have less of a chance of getting sick from a contaminated spice than a contaminated fruit or vegetable, for example.
Still, the agency has targeted spices because their route to a diner's plate is so circuitous and the potential for contamination comes at many different points. Most all of the spices eaten in the United States are imported, and most come from small farms in a variety of countries that all have different levels of food safety oversight.
The report says spices are produced by a wide variety of agricultural practices, including "on very small farms where farm animals are used to plow, crops are harvested by hand, and spices are dried in open air." All of these practices have potential for animal, bird or human contamination. Off the farm, spices from the small farms are often combined, sold to exchanges or packing companies, or stored for years, increasing the chances that they are temporarily in unclean circumstances.
The study looked at spices imported from several countries, with many of the shipments coming from India, Mexico, Thailand and Vietnam.
Michael Taylor, FDA's deputy commissioner for foods, says the agency is "not recommending that consumers stay away from spices," though the chances of someone getting sick can be reduced by adding spices to food before it is cooked.
Taylor says that food safety rules proposed earlier this year aiming to make imported and domestic food safer on farms and in processing facilities should help reduce spice contamination. The proposed rules include regulations that will require food importers to better understand where the food they bring into the country has been.
According to the study, much of the knowledge and technology to reduce contamination exist but are often not used. It surmised that problems arose because of generally unhygienic conditions, including the failure to limit animal and insect access to food and not taking steps like irradiation to kill any potential pathogens.
The report said that better training across the spice supply chain would be one way to reduce illnesses.
___
Follow Mary Clare Jalonick on Twitter: http://twitter.com/mcjalonick
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